CO-CODAMOL

Posology Adults:

Two tablets not more frequently than every four to six hours, when necessary, up to a maximum of 8 tablets in 24 hours.

Elderly:

As for adults, however, a reduced dose may be required. The dose should not be repeated more frequently than every four hours for adults. Not more than 4 doses should be administered in any 24-hour period.

Paediatric Population:

Children aged 16 - 18 years: Take one to two tablets every six hours, when necessary, up to a maximum of 8 tablets in 24 hours.

Children aged 12 - 15 years:

Take one tablet every six hours, when necessary, up to a maximum of 4 tablets in 24 hours. The dose should not be repeated more frequently than every six hours for children over 12 years. Not more than 4 doses should be administered in any 24-hour period.

Duration of treatment The duration of treatment should be limited to 3 days or as short as possible and if no effective pain relief is achieved the patients/carers should be advised to seek the views of a healthcare professional. 1.

4). Method of administration Oral administration only Treatment goals and discontinuation Before initiating treatment with Co-codamol 8 mg/500 mg tablets, treatment duration and treatment goals should be agreed together with the patient, in accordance with pain management guidelines.

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is then stopped. Prolonged use of a painkiller for headaches can make them worse. a) Paracetamol: Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure.

Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dos and considered attributable are tabulated below by system class. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Post marketing data Body System Undesirable effect Blood and lymphatic system disorders Thrombocytopenia Agranulocytosis Immune system disorders Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes and angioedema Respiratory, thoracic and mediastinal disorders Bronchospasm* Hepatobiliary disorders Hepatic dysfunction Skin and subcutaneous tissue disorders Very rare cases of serious skin reactions have been reported.

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs. b) Codeine: Less frequent effects are nausea, vomiting, sweating, facial flushing, dry mouth, blurred or double vision, dizziness, orthostatic hypotension, malaise, tiredness, headache, anorexia, vertigo, bradycardia, palpitations, respiratory depression, dyspnoea, allergic reactions (itch, skin rash, facial oedema) and difficulties in micturition (dysuria, increased frequency, decrease in amount).

Side effects which occur rarely include convulsions, hallucinations, nightmares, uncontrolled muscle movements, muscle rigidity, mental depression and stomach cramps. Drug dependence Repeated use of Co-codamol 8 mg/500 mg tablets can lead to drug dependence, even at therapeutic doses.

4). 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients. Sphincter of Oddi dysfunction Frequency ‘Not known’ Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

Care should be observed in administering the product to any patient, whose condition may be exacerbated by opioids, including the elderly, who may be sensitive to their central and gastro-intestinal effects, those on concurrent CNS depressant drugs, those with prostatic hypertrophy, hypothyroidism and those with inflammatory or obstructive bowel disorders, Addison's disease or myasthenia gravis.

Care should also be observed if prolonged therapy is contemplated. , chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended.

The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors. Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. CYP2D6 metabolism Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite.

If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses.

These patients convert codeine into morphine rapidly resulting in higher-than- expected serum morphine levels. General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite.

In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. 9% Northern European 1%-2% 3. 3). All children received doses of codeine that were within the appropriate dose range; however, there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

4. Children with compromised respiratory function Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures.

These factors may worsen symptoms of morphine toxicity. Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as Co-codamol 8 mg/500 mg tablets.

Repeated use of Co- codamol 8 mg/500 mg tablets can lead to OUD. A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Co-codamol 8 mg/500 mg tablets may result in overdose and/or death.

g. major depression, anxiety and personality disorders). The patient should be made aware of the risks and signs of OUD as set out in the package leaflet. If these signs occur, patients should contact their physician. For patients who experience signs and symptoms of OUD, and/or exhibit drug seeking behaviours, review of concomitant opioids and psycho-active drugs (like benzodiazepines) and consultation with an addiction specialist may be required.

Hepatobiliary disorders Codeine may cause dysfunction and spasm of the sphincter of Oddi, thus increasing the risk of biliary tract symptoms and pancreatitis. Therefore, codeine/paracetamol has to be administered with caution in patients with pancreatitis and diseases of the biliary tract.

Hyperalgesia As with other opioids, in case of insufficient pain control in response to an increased dose of codeine, the possibility of opioid-induced hyperalgesia should be considered. A dose reduction or treatment review may be indicated.

5.

The leaflet will state in:

Headlines Section (to be prominently displayed) • This medicine can only be used for the short-term relief of moderate pain that is not relieved by other painkillers such as paracetamol or ibuprofen alone. • You should only take this product for a maximum of three days at a time.

If you need to take it for longer than three days you should see your doctor or pharmacist for advice. • This medicine contains codeine which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it.

• If you take this medicine for headaches for more than three days, it can make them worse.

Section 1:

What the medicine is for For the short-term relief of moderate pain that […]

4). 6). • In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers. a) Paracetamol: Known hypersensitivity to Paracetamol or any of the constituents. b) Codeine • Known hypersensitivity to Codeine or other opioid analgesics • Moderate to severe renal failure • Moderate to severe liver disease • Respiratory depression and obstructive airways disease • Bronchial asthma attack or heart failure secondary to chronic lung disease • Raised intracranial pressure, head injuries and acute alcoholism • Diarrhoea associated with pseudomembranous colitis.

Diarrhoea caused by poisoning until toxic material has been eliminated from gastrointestinal tract. 2.